Maternal cocaine use has emerged as a major public health issue. Surveys of primarily inner city populations indicate that 10-15% of women use cocaine sometime during pregnancy. The drug readily crosses the placenta and leads to both cerebral structural and neurobehavioral abnormalities in the unborn infant. The mechanisms of these abnormalities are not known. A major goal of this research is to identify mechanisms underlying the structural and functional effects of cocaine exposure in utero on the fetal brain. The objectives of this proposal are three-fold. First, using the fetal sheep as an animal model, the effects of cocaine on fetal cerebral blood flow and cerebral oxygen delivery will be described. Although the fetus becomes hypoxic after maternal cocaine use, preliminary studies show that cerebral blood flow increases so that oxygen delivery to the tissue may be unimpaired. Fetal cerebral blood flow, oxygen delivery, and metabolic rate for oxygen before and after both maternal cocaine administration and direct fetal administration of cocaine will be investigated. Cerebral blood flow will be measured using both the radiolabeled microsphere method and our own newly designed heated thermocouple technique. Secondly, cocaine's effects on some important structural and functional aspects of the developing brain will be determined. Local cerebral glucose metabolism, local cerebral protein synthesis, and behavioral states will be studied in fetuses exposed to cocaine and under control circumstances. Thirdly, the relationship between gestational age and cocaine exposure on these structural and functional aspects of the developing brain will be investigated. It is anticipated that structural and functional alterations due to cocaine exposure will be very different in immature brains undergoing rapid growth compared to more mature central nervous systems. Thus, studies will be performed at two gestational ages, one of rapid brain growth and one nearer maturity.